Tumor angiogenesis is the formation of capillary sprouts induced by a group of tumor cells. These sprouts eventually develop into a microcirculatory network within the tumor mass. There are two principle types of tumor angiogenesis in terms of the events which follow implantations of metastatic seedlings on surfaces and in organs.
The first or primary angiogenesis is the initial vascularization of the mass of multiplying tumor cells and is regarded as an essential prerequisite for the survival and further growth of a metastatic deposit.
The second is the continuing or secondary angiogenesis and is the phenomenon which occurs in waves at the periphery of a growing tumor mass. This secondary angiogenesis is essential for the accretion of new microcirculatory territories into the service of the expanding and infiltrating tumor.
Other types of angiogenesis not associated with tumor formation or growth are found in the development of retinopathy, psoriasis and rheumatoid arthritis (pannus formation). Several different research groups have purified angiogenesis factors from different disease states.
It is apparent that a chemical which would inhibit angiogenesis, eigher by competitively inhibiting an angiogenesis factor or by some other mechanism, would have an adverse effect upon the growth of tumors, on the development of retinopathy or rheumatoid arthritis, or on the development of the psoriatic lesion. It is an object of this invention to provide a group of compounds which inhibit angiogenesis wherever found.